Prioritising Cholera Vaccinations During Cholera Outbreaks

Cholera is an acute diarrheal infection caused by toxigenic strains of Vibro cholerae, with a short incubation period of two hours to five days that enables rapid spread through fecal contamination of water and food sources (Asantewaa et al, 2024).

Despite being preventable and treatable, cholera continues to impose a substantial global health burden, with estimates indicating approximately 2.9 million cases and up to 95,000 deaths occurring annually worldwide (Ali et al, 2015). The global distribution of cholera burden is highly unequal, with approximately 1.3 billion people living at risk in endemic countries, and Sub-Saharan Africa bearing the majority of this burden (Ali et al, 2015). Recent years have witnessed some of the most severe outbreaks in recorded history, with 2017 marking a particularly devastating year due to major outbreaks in Yemen, the Democratic Republic of Congo, Nigeria, Somalia and South Sudan (White et al, 2022).

Global cholera cases more than doubled from 2021, with over 600,000 cases and roughly 7,600 deaths reported in 2024 alone across 33 countries (WHO, 2025). In October 2024, the global stockpile of oral cholera vaccine (OCV) ran completely dry (Houston & Houston, 2025). Supply has since recovered substantially. Annual production reached approximately 70 million doses in 2025, up from 35 million in 2022 (WHO, 2026).

OCV in outbreaks is most effective when it is geographically targeted to where transmission risk is highest (e.g., displaced populations, dense informal settlements, flood-affected communities) and delivered fast enough to reduce onward spread, while not diverting resources from the core pillars of cholera control: case management (rapid rehydration), safe water/sanitation, and risk communication (WHO, 2017).

Effective prioritisation rests on 1. geographic targeting of hotspots, and 2. population-level risk stratification within those hotspots. Geographic targeting strategies rely heavily on surveillance data to identify high-risk areas for vaccination campaigns.

Population-level prioritisation, when vaccine supply is constrained, follows a risk hierarchy informed by age, health status, and living conditions. The highest priority groups include:

• Children aged 1-5 years, who face the highest cholera mortality rates globally and for whom single-dose protection wanes most rapidly, with vaccine effectiveness dropping to roughly 33% by year three versus sustained protection in older individuals (Malembaka et al, 2024). However, limiting vaccination to children aged 1-5 years can be less effectives because vaccine efficiency is lower among young children, therefore evidence suggests the optimal strategy is to prioritise older children (5-14 years), irrespective of setting and level of vaccination (Leung et al, 2021).
• Displaced populations in refugee and IDP camps, where attack rates of 1-5% are common and WASH infrastructure is often lacking or absent (IFRC, 2025).
• Urban slum dwellers, particularly in peri-urban areas lacking sanitation infrastructure, where the WHO identifies typical at-risk areas (Talavera & Pérez, 2009).
• Women are more at risk than men. For example, women in the Somali Region of Ethiopia were more than four times as likely to die from the Cholera epidemic of 2017 compared to men (Hassen & Warfa, 2026)
• Pregnant women and immunocompromised individuals (including those with HIV), for whom OCV is safe and the risk-benefit ration strongly favours vaccination (Global Task Force on Cholera Control, 2026).
• Elderly populations over 65 years who exhibit case fatality rates 5-10 times higher than younger adults in historical data.

Ring vaccination strategies offer a promising targeted approach, particularly in urban settings. Since Cholera cases tend to cluster in time and place, particularly among household contacts of a cholera case, ring vaccination around cases could be considered (Deen & Clemens, 2021) (Sugimoto et al, 2014). Evidence shows that high-level protection can be achieved for those living close to cholera cases (Deen & Clemens, 2021) (Ali et al, 2016). Modelling studies demonstrate vaccinating people within 100m around index case households and improving their water source early in epidemics could reduce the number of cases by 82% compared to uncontrolled epidemics (Deen & Clemens, 2021) (Finger et al, 2018) (von Seidlein & Deen, 2018)

The timing of cholera vaccination campaigns is crucial for maximising their impact, with rapid deployment being the most important factor for success. Delayed response can still provide substantial benefits, particularly in prolonged outbreaks. If circumstances prevent a rapid response there are good reasons to roll out cholera mass vaccination campaigns well into the outbreak (Reyburn et al, 2011). The key threshold appears to be implementation within the first few months, as reactive vaccination campaigns can be implemented within the first few months of an epidemic to maintain effectiveness (Morre & Lessler, 2015).

Pre-emptive vaccination strategies offer the greatest potential impact by preventing outbreaks before they begin. Pre-emptive vaccination should be considered by local health authorities to help prevent potential outbreaks or the spread of current outbreaks to new areas (López-Gigosos et al, 2011). This approach is particularly valuable when strategic timing of vaccination programmes, ideally preceding the expected cholera peak seasons, could significantly enhance control outcomes (Gyamfi, 2025). In conflict settings, integrating vaccination strategies in emergency responses plans, ideally before the projected outbreak peaks, particularly when risk factors such as water shortage and displacement are prominent, can prevent large-scale transmission (Azhary et al, 2025).

The choice between pre-emptive and reactive vaccination depends on several factors. The optimal allocation of vaccine doses between endemic and epidemic settings depends on five factors (Moore et al, 2015):

1. The expected size of the epidemic
2. The amount of time it will take to begin the reactive vaccinationcampaign in the epidemic setting
3. The estimated size of the population at risk of infection in the epidemic setting
4. The number of doses remaining in the stockpile
5. The time horizon over which we compare performance

Implementation flexibility is essential for campaign management. Both pre-emptive and reactive approaches should cover as many people as possible and should be conducted as quickly as possible to maximise their effectiveness (López-Gigosos et al, 2011).

The fundamental decision in cholera vaccination during outbreaks is choosing between single-dose and two-dose strategies, with single-dose approaches increasingly recommended when vaccine supplies are limited. In outbreaks, a single-dose strategy may be considered for short-term protection (Sekhar & Kang, 2020). This approach is particularly valuable because healthcare organisations recommend adopting a single-dose strategy instead of a two-dose strategy. Though the efficacy of a single-dose is lower, it provides coverage and rapidly protects as many of the at-risk population as possible, which may avert more cases and deaths when vaccine supplies are limited (Qasem et al, 2022).

The timing of vaccination initiation significantly influences the optimal dosing strategy. For reactive vaccination, a trade-off between timing and effectiveness was revealed. A single dose approach may be nearly or more effective than vaccinating fewer individuals with a complete two-dose programme assuming conservative vaccine effectiveness estimates (Havumaki et al, 2019). The populations previous cholera exposure history should also inform dosing decisions. When OCVs are used for the control of an outbreak in a known high-endemicity hotspot and/or late in an outbreak, it may be practical and cost-effective to use a single-dose OCV in order to maximise the number of individuals reached with a first dose (Holmgren, 2021).

Logistical constraints often favour single-dose approaches during outbreak responses. This consideration is particularly important if vaccination occurs later in the outbreak, where rapid protection is needed. Given current global constraints, including global OCV shortages, there is an urgent need for each country reporting cholera outbreaks to be strategic on how vaccines are to be deployed (Chisenga et al, 2024).

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